细胞治疗在慢性移植物抗宿主病中的研究新视野

New perspectives in the research of cell therapy in chronic graft-versus-host disease

  • 摘要: 慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植后影响患者长期生存的主要挑战,尤其对激素耐药患者缺乏有效治疗手段。近年来,细胞疗法作为“活药物”,通过主动免疫调节而非传统广谱免疫抑制,为cGVHD治疗带来突破。间充质干细胞在降低cGVHD发生率和治疗难治性患者中显示出潜力,但其疗效受细胞来源与异质性影响;调节性T细胞(Treg)在重建免疫耐受方面表现突出,并逐步向抗原特异性及嵌合抗原受体(CAR)-Treg等精准方向演进;此外,靶向致病性B细胞、浆细胞或成纤维细胞的CAR-T细胞疗法,以及调节性B细胞、髓系来源抑制细胞等新型策略,进一步拓展了治疗路径。尽管面临产品标准化、疗效预测与成本等挑战,未来通过联合用药、通用型产品及基因工程技术的融合,细胞治疗有望推动cGVHD迈向个体化、精准化治疗新时代。

     

    Abstract: Chronic graft-versus-host disease (cGVHD) is a major challenge affecting the long-term survival of patients after allogeneic hematopoietic stem cell transplantation, especially for those who are resistant to glucocorticoid. In recent years, cell therapy, as an "active drug", has brought breakthroughs in the treatment of cGVHD by actively regulating immunity rather than using traditional broad-spectrum immunosuppression. Mesenchymal stem cells have shown potential in reducing the incidence of cGVHD and treating refractory patients, but their efficacy is affected by the cell source and heterogeneity; regulatory T cell (Treg) has performed outstandingly in restoring immune tolerance and are gradually evolving towards antigen-specific and chimeric antigen receptor (CAR)-Treg in a precise direction; in addition, CAR-T cell therapies targeting pathogenic B cell, plasma cell, or fibroblast, as well as novel strategies such as regulatory B cell and myeloid-derived suppressor cell, have further expanded the treatment options. Despite challenges such as product standardization, efficacy prediction and cost, in the future, through the integration of combination therapy, universal products and genetic engineering technologies, cell therapy is expected to drive cGVHD towards an individualized and precise treatment era.

     

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